Acupuncture and neuroregeneration in ischemic stroke

Acupuncture is potentially beneficial for post-stroke rehabilitation and is considered a promising preventive strategy for stroke.Electroacupuncture pretreatment or treatment after ischemic stroke by using appropriate electroacupuncture parameters generates neuroprotective and neuroregenerative effects that increase cerebral blood flow,regulate oxidative stress,attenuate glutamate excitotoxicity,maintain bloodbrain barrier integrity,inhibit apoptosis,increase growth factor production,and induce cerebral ischemic tolerance.

Neuroregeneration and plasticity: a review of the physiological mechanisms for achieving functional recovery postinjury

Neuronal networks,especially those in the central nervous system(CNS),evolved to support extensive functional capabilities while ensuring stability.Several physiological"brakes"that maintain the stability of the neuronal networks in a healthy state quickly become a hinderance postinjury.These"brakes"include inhibition from the extracellular environment,intrinsic factors of neurons and the control of neuronal plasticity.There are distinct differences between the neuronal networks in the peripheral nervous system(PNS)and the CNS.Underpinning these differences is the trade-off between reduced functional capabilities with increased adaptability through the formation of new connections and new neurons.The PNS has"facilitators"that stimulate neuroregeneration and plasticity,while the CNS has"brakes"that limit them.By studying how these"facilitators"and"brakes"work and identifying the key processes and molecules involved,we can attempt to apply these theories to the neuronal networks of the CNS to increase its adaptability.The difference in adaptability between the CNS and PNS leads to a difference in neuroregenerative properties and plasticity.Plasticity ensures quick functional recovery of abilities in the short and medium term.Neuroregeneration involves synthesizing new neurons and connections,providing extra resources in the long term to replace those damaged by the injury,and achieving a lasting functional recovery.Therefore,by understanding the factors that affect neuroregeneration and plasticity,we can combine their advantages and develop rehabilitation techniques.Rehabilitation training methods,coordinated with pharmacological interventions and/or electrical stimulation,contributes to a precise,holistic treatment plan that achieves functional recovery from nervous system injuries.Furthermore,these techniques are not limited to limb movement,as other functions lost as a result of brain injury,such as speech,can also be recovered with an appropriate training program.

The brain-derived neurotrophic factor in neuronal plasticity and neuroregeneration: new pharmacological concepts for old and new drugs

Neurotrophins：Neurotrophins are peptides or proteins that are known to regulate neuronal viability,development,and function Beyond synaptic plasticity,neurotrophins protect neurons from apoptosis and also promote neurogenesis to recover neuronal defici even in adulthood.

SNARE complex in axonal guidance and neuroregeneration

Through complex mechanisms that guide axons to the appropriate routes towards their targets, axonal growth and guidance lead to neuronal system formation. These mechanisms establish the synaptic circuitry necessary for the optimal performance of the nervous system in all organisms. Damage to these networks can be repaired by neuroregenerative processes which in turn can re-establish synapses between injured axons and postsynaptic terminals. Both axonal growth and guidance and the neuroregenerative response rely on correct axonal growth and growth cone responses to guidance cues as well as correct synapses with appropriate targets. With this in mind, parallels can be drawn between axonal regeneration and processes occurring during embryonic nervous system development. However, when studying parallels between axonal development and regeneration many questions still arise; mainly, how do axons grow and synapse with their targets and how do they repair their membranes, grow and orchestrate regenerative responses after injury. Major players in the cellular and molecular processes that lead to growth cone development and movement during embryonic development are the Soluble N-ethylamaleimide Sensitive Factor （NSF） Attachment Protein Receptor （SNARE） proteins, which have been shown to be involved in axonal growth and guidance. Their involvement in axonal growth, guidance and neuroregeneration is of foremost importance, due to their roles in vesicle and membrane trafficking events. Here, we review the recent literature on the involvement of SNARE proteins in axonal growth and guidance during embryonic development and neuroregeneration.

Purinergic signalling in neuroregeneration

Purinergic signalling,adenosine 5′-triphosphate（ATP）as an extracellular signalling molecule,was proposed in 1972（Burnstock,1972）.However,it was not generally accepted until the early 1990s when receptors for ATP and its breakdown product adenosine were cloned and characterised（Ralevic and Burnstock,1998）.Four P1（adenosine）receptors are recognised（A1,A2A,A2B and A3）.

Neuroregeneration using in vivo cellular reprogramming

Cellular reprogramming is an innovative technology used to artificlally convert a mature cell type into a different cell type by molecular＇manipulation. The general concept of cellular reprogramming is to use master transcription factors to override the endogenous transcriptome profile of a given cell type with the transcriptome profile of the target cell type, thereby altering the cellular function and identity.

eural Regeneration Research-- An interesting SCI-indexed journal in neuroregeneration

Neural Regeneration Research （NRR） is an international academic journal specialized in the field of neural regeneration research and published in English. The journal is supervised by the Ministry of Health, P.R. China, sponsored by the Chinese Association of Rehabilitation Medicine, and co-edited by the Editorial Department of Neural Regeneration Research and China Science Press.

Neural Regeneration Research--An interesting SCI-indexed journal in neuroregeneration

Neural Regeneration Research （NRR） is an international academic journal specialized in the field of neural regeneration research and published in English. The journal is supervised by the Ministry of Health, P.R. China, sponsored by the Chinese Association of Rehabilitation Medicine, and co-edited by the Editorial Department of Neural Regeneration Research and China Science Press.

Neuroregeneration in the visual cortex

Totally three articles focusing on “the expression of Nogo-A, Nogo receptor and NADPH-diaphorase in the developing rat visual cortex and the effects of levodopa methyl ester on nerve growth factor expression in visual cortex area 17 in strabismic amblyopia” are published in three issues. We hope that our readers find these papers useful to their research.

Editor's Choice——Experimental autoimmune encephalomyelitis and neuroregeneration

An experimental autolmmune encephalomyelitis model can be used to mimic pathological changes of multiple sclerosis from different angles. During the acute phase of experimental autolmmune encephalomyelitis, CD4＋ T-cells in the central nervous system infiltrate, proliferate, release large amounts of pro-inflammatory cytokines, and activate the inflammatory cascade, which ultimately leads to

How does zebrafish support new strategies for neuroprotection and neuroregeneration in hypoxia-related diseases?

Hypoxia is a condition found commonly in several disorders,such as ischemia,asthma,anemia and neonatal hypoxia.Individuals subjected suddenly to high altitude or extreme exercise are also challenged to low oxygen（O2）levels.Since the brain presents elevated basal O_2 consumption,this organ is readily affected by hypoxia.For this reason,

Interplay between mesenchymal stromal cells and the immune system after transplantation: implications for advanced cell therapy in the retina

Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration,namely trophic factor deprivation and neuroinflammation.Most studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional improvement.However,little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous system.Here,we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system,focusing on recent work in the retina and the importance of the type of transplantation.

Stiffness-tunable biomaterials provide a good extracellular matrix environment for axon growth and regeneration

Neuronal growth, extension, branching, and formation of neural networks are markedly influenced by the extracellular matrix—a complex network composed of proteins and carbohydrates secreted by cells. In addition to providing physical support for cells, the extracellular matrix also conveys critical mechanical stiffness cues. During the development of the nervous system, extracellular matrix stiffness plays a central role in guiding neuronal growth, particularly in the context of axonal extension, which is crucial for the formation of neural networks. In neural tissue engineering, manipulation of biomaterial stiffness is a promising strategy to provide a permissive environment for the repair and regeneration of injured nervous tissue. Recent research has fine-tuned synthetic biomaterials to fabricate scaffolds that closely replicate the stiffness profiles observed in the nervous system. In this review, we highlight the molecular mechanisms by which extracellular matrix stiffness regulates axonal growth and regeneration. We highlight the progress made in the development of stiffness-tunable biomaterials to emulate in vivo extracellular matrix environments, with an emphasis on their application in neural repair and regeneration, along with a discussion of the current limitations and future prospects. The exploration and optimization of the stiffness-tunable biomaterials has the potential to markedly advance the development of neural tissue engineering.

Annexin A1 in the nervous and ocular systems

The therapeutic potential of Annexin A1,an important member of the Annexin superfamily,has become evident in results of experiments with multiple human systems and animal models.The anti-inflammatory and pro-resolving effects of Annexin A1 are characteristic of pathologies involving the nervous system.In this review,we initially describe the expression sites of Annexin A1,then outline the mechanisms by which Annexin A1 maintains the neurological homeostasis through either formyl peptide receptor 2 or other molecular approaches;and,finally,we discuss the neuroregenerative potential qualities of Annexin A1.The eye and the nervous system are anatomically and functionally connected,but the association between visual system pathogenesis,especially in the retina,and Annexin A1 alterations has not been well summarized.Therefore,we explain the beneficial effects of Annexin A1 for ocular diseases,especially for retinal diseases and glaucoma on the basis of published findings,and we explore present and future delivery strategies for Annexin A1 to the retina.

Novel therapeutic strategies targeting mitochondria as a gateway in neurodegeneration

In recent years, multiple disciplines have focused on mitochondrial biology and contributed to understanding its relevance towards adult-onset neurodegenerative disorders. These are complex dynamic organelles that have a variety of functions in ensuring cellular health and homeostasis. The plethora of mitochondrial functionalities confers them an intrinsic susceptibility to internal and external stressors(such as mutation accumulation or environmental toxins), particularly so in long-lived postmitotic cells such as neurons. Thus, it is reasonable to postulate an involvement of mitochondria in aging-associated neurological disorders, notably neurodegenerative pathologies including Alzheimer’s disease and Parkinson’s disease. On the other hand, biological effects resulting from neurodegeneration can in turn affect mitochondrial health and function, promoting a feedback loop further contributing to the progression of neuronal dysfunction and cellular death. This review examines state-of-the-art knowledge, focus on current research exploring mitochondrial health as a contributing factor to neuroregeneration, and the development of therapeutic approaches aimed at restoring mitochondrial homeostasis in a pathological setting.

A benchtop brain injury model using resected donor tissue from patients with Chiari malformation

The use of live animal models for testing new therapies for brain and spinal cord repair is a controversial area. Live animal models have associated ethical issues and scientific concerns regarding the predictability of human responses. Alternative models that replicate the 3 D architecture of the central nervous system have prompted the development of organotypic neural injury models. However, the lack of reliable means to access normal human neural tissue has driven reliance on pathological or post-mortem tissue which limits their biological utility. We have established a protocol to use donor cerebellar tonsillar tissue surgically resected from patients with Chiari malformation(cerebellar herniation towards the foramen magnum, with ectopic rather than diseased tissue) to develop an in vitro organotypic model of traumatic brain injury. Viable tissue was maintained for approximately 2 weeks with all the major neural cell types detected. Traumatic injuries could be introduced into the slices with some cardinal features of post-injury pathology evident. Biomaterial placement was also feasible within the in vitro lesions. Accordingly, this ‘proof-of-concept’ study demonstrates that the model offers potential as an alternative to the use of animal tissue for preclinical testing in neural tissue engineering. To our knowledge, this is the first demonstration that donor tissue from patients with Chiari malformation can be used to develop a benchtop model of traumatic brain injury. However, significant challenges in relation to the clinical availability of tissue were encountered, and we discuss logistical issues that must be considered for model scale-up.

Hypoxic preconditioning stimulates angiogenesis in ischemic penumbra after acute cerebral infarction

Previous studies have demonstrated the protective effect of hypoxic preconditioning on acute cerebral infarction, but the mechanisms underlying this protection remain unclear. To investigate the protective mechanisms of hypoxic preconditioning in relation to its effects on angiogenesis, we in- duced a photochemical model of cerebral infarction in an inbred line of mice （BALB/c）. Mice were then exposed to hypoxic preconditioning 30 minutes prior to model establishment. Results showed significantly increased vascular endothelial growth factor and CD31 expression in the ischemic penumbra at 24 and 72 hours post infarction, mainly in neurons and vascular endothelial cells. Hypoxic preconditioning increased vascular endothelial growth factor and CD31 expression in the ischemic penumbra and the expression of vascular endothelial growth factor was positively related to that of CD31. Moreover, hypoxic preconditioning reduced the infarct volume and improved neu- rological function in mice. These findings indicate that the protective role of hypoxic preconditioning in acute cerebral infarction may possibly be due to an increase in expression of vascular endothelial growth factor and CD31 in the ischemic penumbra, which promoted angiogenesis.

Xueshuantong improves cerebral blood perfusion in elderly patients with lacunar infarction

A total of 64 patients with acute lacunar infarction were enrolled within 24 hours of onset. The patients received conventional therapy （antiplatelet drugs and hypolipidemic drugs） alone or conventional therapy plus 450 mg Xueshuantong once a day. The main ingredient of the Xueshuantong lyophilized powder used for injection was Panax notoginseng saponins. Assessments were made at admission and at discharge using the National Institutes of Health Stroke Scale, the Activity of Daily Living and the Mini-Mental State Examination. Additionally, the relative cerebral blood flow, relative cerebral blood volume and relative mean transit time in the region of interest were calculated within 24 hours after the onset of lacunar infarction, using dynamic susceptibility contrast magnetic resonance perfusion imaging technology. Patients underwent a follow-up MRI scan after 4 weeks of treatment. There was an improvement in the Activity of Daily Living scores and a greater reduction in the scores on the National Institutes of Health Stroke Scale in the treatment group than in the control group. However, the Mini-Mental State Examination scores showed no significant differences after 4 weeks of treatment. Compared with the control group, the relative cerebral blood flow at discharge had increased and showed a greater improvement in the treatment group. Furthermore, there was a reduction in the relative mean transit time at discharge and the value was lower in the treatment group than in the control group. The experimental findings indicate that Xueshuantong treatment improves neurological deficits in elderly patients with lacunar infarction, and the mechanism may be related to increased cerebral perfusion.

Mild hypothermia as a treatment for central nervous system injuries Positive or negative effects?

Besides local neuronal damage caused by the primary insult, central nervous system injuries may secondarily cause a progressive cascade of related events including brain edema, ischemia, oxida- tive stress, excitotoxicity, and dysregulation of calcium homeostasis. Hypothermia is a beneficial strategy in a variety of acute central nervous system injuries. Mild hypothermia can treat high in- tracranial pressure following traumatic brain injuries in adults. It is a new treatment that increases survival and quality of life for patients suffering from ischemic insults such as cardiac arrest, stroke, and neurogenic fever following brain trauma. Therapeutic hypothermia decreases free radical pro- duction, inflammation, excitotoxicity and intracranial pressure, and improves cerebral metabolism after traumatic brain injury and cerebral ischemia, thus protecting against central nervous system damage. Although a series of pathological and physiological changes as well as potential side ef- fects are observed during hypothermia treatment, it remains a potential therapeutic strategy for central nervous system injuries and deserves further study.

Olive leaf extract inhibits lead poisoning-induced brain injury

Olive leaves have an antioxidant capacity, and olive leaf extract can protect the blood, spleen and hippocampus in lead-poisoned mice. However, little is known about the effects of olive leaf extract on lead-induced brain injury. This study was designed to determine whether olive leaf extract can inhibit lead-induced brain injury, and whether this effect is associated with antioxidant capacity. First, we established a mouse model of lead poisoning by continuous intragastric administration of lead acetate for 30 days. Two hours after successful model establishment, lead-poisoned mice were given olive leaf extract at doses of 250, 500 or 1 000 mg/kg daily by intragastric administration for 50 days. Under the transmission electron microscope, olive leaf extract attenuated neuronal and capillary injury and reduced damage to organelles and the matrix around the capillaries in the frontal lobe of the cerebral cortex in the lead-poisoned mice. Olive leaf extract at a dose of 1 000 mg/kg had the greatest protective effect. Spectrophotometry showed that olive leaf extract significantly in- creased the activities of superoxide dismutase, catalase, alkaline phosphatase and acid phes- phatase, while it reduced malondialdehyde content, in a dose-dependent manner. Furthermore, immunohistochemical staining revealed that olive leaf extract dose-dependently decreased Bax protein expression in the cerebral cortex of lead-poisoned mice. Our findings indicate that olive leaf extract can inhibit lead-induced brain injury by increasing antioxidant capacity and reducing apop- tosis.